Appetite Hormones in Binge Eating Disorder

描述(由申请者提供)：肥胖症在全球范围内继续上升。相当一部分肥胖受试者有暴饮暴食障碍(床)，并摄入大量食物，而没有清除神经性暴食症。床是最常见的饮食障碍，会导致许多痛苦和痛苦。还有一群研究不足的瘦床患者，面临肥胖的风险。通过包括它们，床的病理生理学可以从肥胖中分离出来。人们对床的心理方面的研究要好于对生物方面的研究。在初步研究中，影响食欲的激素存在差异，特别是刺激食欲的胃促生长素，在固定的早餐前，胃促生长素水平较低，而肥胖床位受试者之后的降幅较小。这一发现是违反直觉的，因为预计Ghrelin会更高。在晚上暴饮暴食的时候，床上的胃促生长素可能比不上床的人高，这是一天中自然增加的。在固定的晚间测试餐之后，床上的胃促生长素也应该有较小的下降，这可能会导致后续更多的食物摄入。在36名卧床受试者和36名非卧床受试者中，按体重和性别平均划分，研究人员将在早晚固定膳食后的2小时内研究与食欲相关的激素，包括Ghrelin，以及饱腹肽GLP-1和PYY。然后，受试者将享受一顿临时晚餐，直到吃饱为止。预计在床上的摄入量会更大，特别是在晚上。另一天将应用社会压力方案(Trier)来提高这些受试者的皮质醇水平。在床上，与更多的饥饿和进食相关的皮质醇反应预计会增强。这种床上病理生理学模型假定进食开始(晚上较高的Ghrelin，以及应激源后较高的皮质醇)和终止进餐(较低的GLP-1，PYY，特别是在晚上)都存在异常。接下来，最有希望的几种急性干预措施将在研究2中实施：a)阻断皮质醇的产生，b)PYY或c)GLP-1治疗。这些研究应该有助于揭示床上的病理生理学，并通过纠正潜在的食欲-激素模式，确定是什么维持了这种紊乱，并为新药治疗提供了基础。公众：这项研究的重点是可能维持暴饮暴食障碍(BED)的食欲激素，这在肥胖者中很常见。然后，我们将尝试纠正最不正常的食欲荷尔蒙，在床上测试一种新的药物治疗方法。

DESCRIPTION (provided by applicant): Obesity continues to increase in prevalence worldwide. A sizable subset of obese subjects has binge eating disorder (BED), and ingest large meals, without the purging of bulimia nervosa. BED, the most common eating disorder, causes much suffering and distress. There is also a group of understudied lean BED individuals, at risk for obesity. By including them, the pathophysiology of BED can be parceled from obesity. The psychological aspects of BED have been better studied than the biological aspects. In preliminary studies, there were differences in hormones influencing appetite, especially ghrelin, which stimulates appetite, with lower ghrelin levels before a fixed morning meal and a smaller decline afterwards in obese BED subjects. This finding was counterintuitive because ghrelin was expected to be higher. It is possible that ghrelin, which naturally increases over the day, is higher in BED than in non-BED individuals in the evening when most binge eating occurs. Following a fixed evening test meal, there should also be a smaller decline in ghrelin in BED, which may lead to more subsequent food intake. In 36 BED and 36 non-BED subjects, equally divided by weight and gender, appetite-related hormones, will be studied, including ghrelin, and the satiety peptides, GLP-1, and PYY, during 2 hours after a fixed meal in the morning and in the evening. Subjects will then have an ad libitum meal until full. The intake is expected to be greater in BED, especially in the evening. A social stress protocol (Trier) will be applied on another day to raise cortisol in these subjects. An enhanced cortisol response associated with greater hunger and meal intake is expected in BED. This model of BED pathophysiology posits abnormalities in both meal initiation (higher ghrelin in evening, and higher cortisol following a stressor) and in meal termination (lower GLP-1, PYY, especially in evening). Next, the most promising of several acute interventions: a) blocking cortisol production, and either b) PYY, or c) GLP-1 administration, will be implemented in Study 2. These studies should help reveal BED pathophysiology, and by correcting a potential disordered appetite-hormone pattern, determine what maintains the disorder, and provide a basis for new drug treatments. Public: This study focuses on appetite hormones that may maintain binge eating disorder (BED), common in obese individuals. We will then attempt to correct the most abnormal appetite hormone to test a new drug treatment approach in BED.